My future research will build on these findings to explore possible involvement of VTA non-DA efferents in updating relationship between stimulus and conditioned response. The goals are to determine which putative targets innervated by VTA non-DA neurons are critically required in discrimination learning, whether chronic use of substance of abuse will dampen discrimination learning and impact selective VTA non-DA efferents and develop an optical intervention technique to rescue learning deficits. Beside my search, I also participate in Dr. Dong Wangs project Median raphe nucleus regulates hippocampal ripple oscillation and memory consolidation. Hippocampal sharp-wave ripples have been the most studied neuronal oscillations and occur primarily during slow-wave sleep and have been shown to play an essential role underlying memory consolidation. A widely held view is that hippocampal ripple oscillations reactivate newly-formed memory traces for long-term storage. Although numerous studies have aimed at addressing the interaction between cortical activities and hippocampal ripple oscillations, causal relationship remains poorly defined. Moreover, little research attention is paid to address whether hippocampal ripple oscillation is subjected to sub-cortical regulation. Here, by combining optogenetics and in vivo simultaneous electrophysiology recordings in freely-moving mice, our study uncovered a novel, unexpected regulatory role of subcortical median raphe nucleus to hippocampal ripple oscillation as well as memory consolidation. Specifically, we first observe ripple-related neuronal activities in median raphe nucleus. To investigate causal relationship, we present evidence that optical stimulation of median raphe suppresses hippocampal ripple activities. Finally, given the causal role of hippocampal ripple oscillation in memory consolidation, we show that optical stimulation of median raphe during sleep impairs hippocampus-dependent fear memory. These data should be of great interest to a wide variety of scientists, as it not only sheds light on the first causal regulatory link from subcortical median raphe toward hippocampal ripple oscillation, but also attribute median raphe the novel function as gatekeeper for ripples and memory consolidation to occur. This work was submitted to Nature and is under revision.

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National Institute on Drug Abuse
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